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. 1989 Dec;84(6):1930–1941. doi: 10.1172/JCI114381

Identification and characterization of a monocyte-derived neutrophil-activating factor in corticosteroid-resistant bronchial asthma.

J R Wilkinson 1, A E Crea 1, T J Clark 1, T H Lee 1
PMCID: PMC304074  PMID: 2556450

Abstract

Peripheral blood mononuclear cells (PBMC) were isolated from seven normal subjects, eight asthmatic subjects clinically sensitive to corticosteroids (CS), and eight asthmatic subjects clinically resistant to corticosteroids (CR). PBMC were cultured at 37 degrees C for 24 h in the absence or presence of 10(-16) to 10(-4) M hydrocortisone. Calcium ionophore (A23187)-activated neutrophils (PMN) primed by supernatants of PBMC from asthmatic subjects cultured in the absence of hydrocortisone generated approximately threefold more leukotriene B4 than PMN primed by supernatants of PBMC from normal subjects (P less than 0.05). Incubation of PBMC derived from CS subjects with 10(-8) M hydrocortisone completely inhibited the production of the enhancing activity (P less than 0.01), whereas in CR subjects hydrocortisone at concentrations up to 10(-4) M did not suppress the release of enhancing activity. The enhancing activity was produced by monocytes. Enhancing activity eluted with an Mr of 3,000 D and a pI of 7.1. It eluted at 10% acetonitrile after reverse-phase HPLC. The activity was destroyed by heating to 60 degrees C for 60 min and was sensitive to pronase treatment. The purified factor also enhanced superoxide generation by PMN which had been stimulated submaximally by phorbol myristate acetate.

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Selected References

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  1. Arm J. P., Spur B. W., Lee T. H. The effects of inhaled leukotriene E4 on the airway responsiveness to histamine in subjects with asthma and normal subjects. J Allergy Clin Immunol. 1988 Oct;82(4):654–660. doi: 10.1016/0091-6749(88)90979-7. [DOI] [PubMed] [Google Scholar]
  2. Arnoux B., Jouvin-Marche E., Arnoux A., Benveniste J. Release of PAF-acether from human blood monocytes. Agents Actions. 1982 Dec;12(5-6):713–716. doi: 10.1007/BF01965089. [DOI] [PubMed] [Google Scholar]
  3. Babior B. M., Kipnes R. S., Curnutte J. T. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest. 1973 Mar;52(3):741–744. doi: 10.1172/JCI107236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bender J. G., McPhail L. C., Van Epps D. E. Exposure of human neutrophils to chemotactic factors potentiates activation of the respiratory burst enzyme. J Immunol. 1983 May;130(5):2316–2323. [PubMed] [Google Scholar]
  5. Bolton A. E., Hunter W. M. The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J. 1973 Jul;133(3):529–539. doi: 10.1042/bj1330529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  7. Carmichael J., Paterson I. C., Diaz P., Crompton G. K., Kay A. B., Grant I. W. Corticosteroid resistance in chronic asthma. Br Med J (Clin Res Ed) 1981 May 2;282(6274):1419–1422. doi: 10.1136/bmj.282.6274.1419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Collins J. V., Clark T. J., Harris P. W., Townsend J. Intravenous corticosteroids in treatment of acute bronchial asthma. Lancet. 1970 Nov 21;2(7682):1047–1049. doi: 10.1016/s0140-6736(70)90283-7. [DOI] [PubMed] [Google Scholar]
  9. Dahinden C. A., Zingg J., Maly F. E., de Weck A. L. Leukotriene production in human neutrophils primed by recombinant human granulocyte/macrophage colony-stimulating factor and stimulated with the complement component C5A and FMLP as second signals. J Exp Med. 1988 Apr 1;167(4):1281–1295. doi: 10.1084/jem.167.4.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dahlén S. E., Björk J., Hedqvist P., Arfors K. E., Hammarström S., Lindgren J. A., Samuelsson B. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3887–3891. doi: 10.1073/pnas.78.6.3887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Damon M., Chavis C., Crastes de Paulet A., Michel F. B., Godard P. Arachidonic acid metabolism in alveolar macrophages. A comparison of cells from healthy subjects, allergic asthmatics, and chronic bronchitis patients. Prostaglandins. 1987 Aug;34(2):291–309. doi: 10.1016/0090-6980(87)90251-6. [DOI] [PubMed] [Google Scholar]
  12. Dessein A. J., Lee T. H., Elsas P., Ravalese J., 3rd, Silberstein D., David J. R., Austen K. F., Lewis R. A. Enhancement by monokines of leukotriene generation by human eosinophils and neutrophils stimulated with calcium ionophore A23187. J Immunol. 1986 May 15;136(10):3829–3838. [PubMed] [Google Scholar]
  13. Drazen J. M., Austen K. F., Lewis R. A., Clark D. A., Goto G., Marfat A., Corey E. J. Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4354–4358. doi: 10.1073/pnas.77.7.4354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. English D., Roloff J. S., Lukens J. N. Chemotactic factor enhancement of superoxide release from fluoride and phorbol myristate acetate stimulated neutrophils. Blood. 1981 Jul;58(1):129–134. [PubMed] [Google Scholar]
  15. Ford-Hutchinson A. W., Bray M. A., Doig M. V., Shipley M. E., Smith M. J. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature. 1980 Jul 17;286(5770):264–265. doi: 10.1038/286264a0. [DOI] [PubMed] [Google Scholar]
  16. Fuller R. W., Kelsey C. R., Cole P. J., Dollery C. T., MacDermot J. Dexamethasone inhibits the production of thromboxane B2 and leukotriene B4 by human alveolar and peritoneal macrophages in culture. Clin Sci (Lond) 1984 Dec;67(6):653–656. doi: 10.1042/cs0670653. [DOI] [PubMed] [Google Scholar]
  17. Goetzl E. J., Pickett W. C. Novel structural determinants of the human neutrophil chemotactic activity of leukotriene B. J Exp Med. 1981 Feb 1;153(2):482–487. doi: 10.1084/jem.153.2.482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gosset P., Tonnel A. B., Joseph M., Prin L., Mallart A., Charon J., Capron A. Secretion of a chemotactic factor for neutrophils and eosinophils by alveolar macrophages from asthmatic patients. J Allergy Clin Immunol. 1984 Dec;74(6):827–834. doi: 10.1016/0091-6749(84)90186-6. [DOI] [PubMed] [Google Scholar]
  19. Joseph M., Tonnel A. B., Torpier G., Capron A., Arnoux B., Benveniste J. Involvement of immunoglobulin E in the secretory processes of alveolar macrophages from asthmatic patients. J Clin Invest. 1983 Feb;71(2):221–230. doi: 10.1172/JCI110762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. KAPLOW L. S. SIMPLIFIED MYELOPEROXIDASE STAIN USING BENZIDINE DIHYDROCHLORIDE. Blood. 1965 Aug;26:215–219. [PubMed] [Google Scholar]
  21. Kay A. B., Diaz P., Carmicheal J., Grant I. W. Corticosteroid-resistant chronic asthma and monocyte complement receptors. Clin Exp Immunol. 1981 Jun;44(3):576–580. [PMC free article] [PubMed] [Google Scholar]
  22. Kronheim S. R., March C. J., Erb S. K., Conlon P. J., Mochizuki D. Y., Hopp T. P. Human interleukin 1. Purification to homogeneity. J Exp Med. 1985 Mar 1;161(3):490–502. doi: 10.1084/jem.161.3.490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lewis R. A., Austen K. F. The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology. J Clin Invest. 1984 Apr;73(4):889–897. doi: 10.1172/JCI111312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lewis R. A., Drazen J. M., Austen K. F., Clark D. A., Corey E. J. Identification of the C(6)-S-conjugate of leukotriene A with cysteine as a naturally occurring slow reacting substance of anaphylaxis (SRS-A). Importance of the 11-cis-geometry for biological activity. Biochem Biophys Res Commun. 1980 Sep 16;96(1):271–277. doi: 10.1016/0006-291x(80)91210-3. [DOI] [PubMed] [Google Scholar]
  25. Lewis R. A., Mencia-Huerta J. M., Soberman R. J., Hoover D., Marfat A., Corey E. J., Austen K. F. Radioimmunoassay for leukotriene B4. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7904–7908. doi: 10.1073/pnas.79.24.7904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lippman M., Barr R. Glucocorticoid receptors in purified subpopulations of human peripheral blood lymphocytes. J Immunol. 1977 Jun;118(6):1977–1981. [PubMed] [Google Scholar]
  27. McPhail L. C., Clayton C. C., Snyderman R. The NADPH oxidase of human polymorphonuclear leukocytes. Evidence for regulation by multiple signals. J Biol Chem. 1984 May 10;259(9):5768–5775. [PubMed] [Google Scholar]
  28. Nagy L., Lee T. H., Goetzl E. J., Pickett W. C., Kay A. B. Complement receptor enhancement and chemotaxis of human neutrophils and eosinophils by leukotrienes and other lipoxygenase products. Clin Exp Immunol. 1982 Mar;47(3):541–547. [PMC free article] [PubMed] [Google Scholar]
  29. Ozaki T., Yasuoka S., Nakayama T., Tsubura E. Glucocorticoid receptors, in human alveolar macrophages and peripheral blood cells. Clin Exp Immunol. 1982 Feb;47(2):505–511. [PMC free article] [PubMed] [Google Scholar]
  30. Palmer R. M., Stepney R. J., Higgs G. A., Eakins K. E. Chemokinetic activity of arachidonic and lipoxygenase products on leuocyctes of different species. Prostaglandins. 1980 Aug;20(2):411–418. doi: 10.1016/s0090-6980(80)80058-x. [DOI] [PubMed] [Google Scholar]
  31. Peck M. J., Piper P. J., Williams T. J. The effect of leukotrienes C4 and D4 on the microvasculature of guinea-pig skin. Prostaglandins. 1981 Feb;21(2):315–321. doi: 10.1016/0090-6980(81)90149-0. [DOI] [PubMed] [Google Scholar]
  32. Peters-Golden M., Bathon J., Flores R., Hirata F., Newcombe D. S. Glucocorticoid inhibition of zymosan-induced arachidonic acid release by rat alveolar macrophages. Am Rev Respir Dis. 1984 Nov;130(5):803–809. doi: 10.1164/arrd.1984.130.5.803. [DOI] [PubMed] [Google Scholar]
  33. Poznansky M. C., Gordon A. C., Douglas J. G., Krajewski A. S., Wyllie A. H., Grant I. W. Resistance to methylprednisolone in cultures of blood mononuclear cells from glucocorticoid-resistant asthmatic patients. Clin Sci (Lond) 1984 Dec;67(6):639–645. doi: 10.1042/cs0670639. [DOI] [PubMed] [Google Scholar]
  34. Rankin J. A., Hitchcock M., Merrill W., Bach M. K., Brashler J. R., Askenase P. W. IgE-dependent release of leukotriene C4 from alveolar macrophages. Nature. 1982 May 27;297(5864):329–331. doi: 10.1038/297329a0. [DOI] [PubMed] [Google Scholar]
  35. Rokach J., Hayes E. C., Girard Y., Lombardo D. L., Maycock A. L., Rosenthal A. S., Young R. N., Zamboni R., Zweerink H. J. The development of sensitive and specific radioimmunoassays for leukotrienes. Prostaglandins Leukot Med. 1984 Jan;13(1):21–25. doi: 10.1016/0262-1746(84)90098-2. [DOI] [PubMed] [Google Scholar]
  36. Roubin R., Elsas P. P., Fiers W., Dessein A. J. Recombinant human tumour necrosis factor (rTNF)2 enhances leukotriene biosynthesis in neutrophils and eosinophils stimulated with the Ca2+ ionophore A23187. Clin Exp Immunol. 1987 Nov;70(2):484–490. [PMC free article] [PubMed] [Google Scholar]
  37. Samuelsson B. Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science. 1983 May 6;220(4597):568–575. doi: 10.1126/science.6301011. [DOI] [PubMed] [Google Scholar]
  38. Schröder J. M., Mrowietz U., Christophers E. Purification and partial biologic characterization of a human lymphocyte-derived peptide with potent neutrophil-stimulating activity. J Immunol. 1988 May 15;140(10):3534–3540. [PubMed] [Google Scholar]
  39. Shaw R. J., Walsh G. M., Cromwell O., Moqbel R., Spry C. J., Kay A. B. Activated human eosinophils generate SRS-A leukotrienes following IgG-dependent stimulation. Nature. 1985 Jul 11;316(6024):150–152. doi: 10.1038/316150a0. [DOI] [PubMed] [Google Scholar]
  40. Smith K. A., Lachman L. B., Oppenheim J. J., Favata M. F. The functional relationship of the interleukins. J Exp Med. 1980 Jun 1;151(6):1551–1556. doi: 10.1084/jem.151.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Snyder D. S., Unanue E. R. Corticosteroids inhibit murine macrophage Ia expression and interleukin 1 production. J Immunol. 1982 Nov;129(5):1803–1805. [PubMed] [Google Scholar]
  42. Vadas M. A., David J. R., Butterworth A., Pisani N. T., Siongok T. A. A new method for the purification of human eosinophils and neutrophils, and a comparison of the ability of these cells to damage schistosomula of Schistosoma mansoni. J Immunol. 1979 Apr;122(4):1228–1236. [PubMed] [Google Scholar]
  43. Werb Z., Foley R., Munck A. Interaction of glucocorticoids with macrophages. Identification of glucocorticoid receptors in monocytes and macrophages. J Exp Med. 1978 Jun 1;147(6):1684–1694. doi: 10.1084/jem.147.6.1684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yaron M., Yaron I., Gurari-Rotman D., Revel M., Lindner H. R., Zor U. Stimulation of prostaglandin E production in cultured human fibroblasts by poly(I)-poly(C) and human interferon. Nature. 1977 Jun 2;267(5610):457–459. doi: 10.1038/267457a0. [DOI] [PubMed] [Google Scholar]
  45. Yip Y. K., Pang R. H., Urban C., Vilcek J. Partial purification and characterization of human gamma (immune) interferon. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1601–1605. doi: 10.1073/pnas.78.3.1601. [DOI] [PMC free article] [PubMed] [Google Scholar]

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